Reconstructing diploid 3D chromatin structures from single cell Hi-C data with a polymer-based approach

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Description of rights: CC-BY-4.0
Item type: Item , ZeitschriftenaufsatzAccess status: Open Access ,

Abstract

Detailed understanding of the 3D structure of chromatin is a key ingredient to investigate a variety of processes inside the cell. Since direct methods to experimentally ascertain these structures lack the desired spatial fidelity, computational inference methods based on single cell Hi-C data have gained significant interest. Here, we develop a progressive simulation protocol to iteratively improve the resolution of predicted interphase structures by maximum-likelihood association of ambiguous Hi-C contacts using lower-resolution predictions. Compared to state-of-the-art methods, our procedure is not limited to haploid cell data and allows us to reach a resolution of up to 5,000 base pairs per bead. High resolution chromatin models grant access to a multitude of structural phenomena. Exemplarily, we verify the formation of chromosome territories and holes near aggregated chromocenters as well as the inversion of the CpG content for rod photoreceptor cells.

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Frontiers in bioinformatics, 3, Frontiers, Lausanne, 2023, https://doi.org/10.3389/fbinf.2023.1284484

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